Purpose: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (nCRT) followed by surgery. Several parameters are associated with patient survival in LARC. One of these parameters is tumor regression grade (TRG); however, the significance of TRG remains controversial. In this study, we aimed to examine the correlations of TRG with 5-year overall (OS) and relapse-free survival (RFS) and identify other factors that influence the survival rates in LARC after nCRT followed by surgery. Methods: This retrospective study included 104 patients diagnosed with LARC who underwent nCRT followed by surgery at Songklanagarind Hospital from January 2010 to December 2015. All patients received fluoropyrimidine-based chemotherapy at a total dose of 45.0 to 50.4 Gy in 25 daily fractions. Tumor response was evaluated using the 5-tier Mandard TRG classification. TRG was categorized into good (TRG 1–2) and poor (TRG 3–5) responses. Results: TRG (classified by either the 5-tier classification system or the 2-group classification system) was not correlated with 5-year OS or RFS. The 5-year OS rates were 80.0%, 54.5%, 80.8%, and 67.4% in patients with TRG 1, 2, 3, and 4, respectively (P=0.22). Poorly differentiated rectal cancer and systemic metastasis were associated with poor 5-year OS. Intraoperative tumor perforation, poor differentiation, and perineural invasion were correlated with inferior 5-year RFS. Conclusion TRG was probably not associated with either 5-year OS or RFS; however, poor differentiation and systemic metastasis were strongly associated with poor 5-year OS.